The US constitution has its quirks but it is crystal clear on one issue: "Congress shall make no law respecting an establishment of religion, or prohibiting the free exercise thereof," begins the first amendment, adopted in 1791. But more than 200 years later, its meaning appears to be lost on Christine O'Donnell, the Tea Party favourite running for a US Senate seat.

At a debate today for the Delaware Senate seat once occupied by Vice President Joe Biden, O'Donnell appeared to be nonplussed by the wording of the first amendment, repeatedly returning to the subject and sounding incredulous after her Democratic opponent Chris Coons attempted to explain it to her.

When Coons told her the text of the constitution prohibited government from establishing any religion, O'Donnell replied in apparent bewilderment: "You're telling me that's in the first amendment?"

Minutes earlier, the audience at Widener Law School in Delaware had laughed in derision when O'Donnell asked: "Where in the constitution is the separation of church and state?"

Not only is the first amendment perhaps the most famous part of the constitution but the "establishment clause", as it is known, is the subject of legal precedent stretching back into the 19th century. No less an authority than Thomas Jefferson declared the clause's aim to build "a wall of separation between church and state".

While O'Donnell's campaign was quick to attempt damage limitation, saying that the words "separation of church and state" appear nowhere in the constitution, the gaffe does O'Donnell no favours as her campaign unravels and she trails far behind Coons in latest opinon polls.

O'Donnell's slip is also the latest in a string of blunders by Tea Party candidates around the US, highlighting the danger of pushing untested candidates under the glare of the national media.

On Sunday, security guards for Republican senate candidate Joe Miller forcibly handcuffed a local journalist after a public event in Alaska, while Nevada Republican Sharron Angle recently told a room full of Hispanic students that "some of you look a little more Asian to me".

• This article was amended on 20 October 2010. The original said that Thomas Jefferson was one of the authors of the US constitution. This has been deleted.